Bioactive Natural Products against Systemic Arterial Hypertension: A Past 20-Year Systematic and Prospective Review.

Background: Systemic arterial hypertension is one of the most common cardiovascular risks, corresponding to 45% of deaths involving CVDs. The use of natural products, such as medicinal plants, belongs to a millennial part of human therapeutics history and has been employed as an alternative anti-hypertensive treatment. Objective: The present review aims to prospect some natural products already experimentally assayed against arterial hypertension through scientific virtual libraries and patent documents over the past 20 years. Search strategy. This is a systematic review of the adoption of the PRISMA protocol and a survey of the scientific literature that synthesizes the results from published articles between 2001 and 2020 concerning the use of medicinal plants in the management of hypertension, including which parts of the plant or organism are used, as well as the mechanisms of action underlying the anti-hypertensive effect. Furthermore, a technological prospection was also carried out in patent offices from different countries in order to check technologies based on natural products claimed for the treatment or prevention of hypertension. Inclusion criteria. Scientific articles where a natural product had been experimentally assayed for anti-hypertensive activity (part of plants, plant extracts, and products derived from other organisms) were included. Data extraction and analysis. The selected abstracts of the articles and patent documents were submitted to a rigorous reading process. Those articles and patents that were not related to anti-hypertensive effects and claimed potential applications were excluded from the search. Results: Eighty specimens of biological species that showed anti-hypertensive activity were recovered, with 01 representative from the kingdom Fungi and 02 from the kingdom Protista, with emphasis on the families Asteraceae and Lamiaceae, with 6 representatives each. Leaves and aerial parts were the most used parts of the plants for the extraction of anti-hypertensive products, with maceration being the most used extraction method. Regarding phytochemical analyses, the most described classes of biomolecules in the reviewed works were alkaloids, terpenes, coumarins, flavonoids, and peptides, with the reduction of oxidative stress and the release of NO among the mechanisms of action most involved in this process. Regarding the number of patent filings, China was the country that stood out as the main one, with 813 registrations. Conclusion: The anti-hypertensive activity of natural products is still little explored in Western countries. Besides, China and India have shown more results in this area than other countries, confirming the strong influence of traditional medicine in these countries.

Biflavones from Platonia insignis Mart. Flowers Promote In Vitro Antileishmanial and Immunomodulatory Effects against Internalized Amastigote Forms of Leishmania amazonensis.

Leishmaniasis is an infectious disease that affects millions of people worldwide, making the search essential for more accessible treatments. The species Platonia insignis Mart. (Clusiaceae) has been extensively studied and has gained prominence for its pharmacological potential. The objective of this work was to evaluate the antileishmania activity, cytotoxic effect and activation patterns of macrophages of hydroalcoholic extract (EHPi), ethyl acetate fractions (FAcOEt) and morelloflavone/volkensiflavone mixture (MB) from P. insignis flowers. EHPi, FAcOEt and MB demonstrated concentration-dependent antileishmania activity, with inhibition of parasite growth in all analyzed concentrations. EHPi exhibited maximum effect at 800 µg/mL, while FAcOEt and MB reduced the growth of the parasite by 94.62% at 800 µg/mL. EHPi, FAcOEt and MB showed low cytotoxic effects for macrophages at 81.78, 159.67 and 134.28 µg/mL, respectively. EHPi (11.25 µg/mL), FAcOEt (11.25 and 22.5 µg/mL) and MB (22.5 µg/mL) characterized the increase in lysosomal activity, suggesting a possible modulating effect. These findings open for the application of flowers from a P. insignis flowers and biflavones mixture thereof in the promising treatment of leishmaniasis.

Antioxidant action and enzyme activity modulation by bioaccessible polyphenols from jambolan (Syzygium cumini (L.) Skeels).

Jambolan is rich in antioxidant polyphenols; however, the bioactivity of these compounds remains poorly investigated. We compared changes in polyphenols and antioxidant capacity by ABTS and FRAP assays of jambolan pulp during in vitro digestion and chemical extraction and evaluated the effects of these changes on oxidative stress in wild and mutant Saccharomyces cerevisiae. Digestion and chemical extraction were performed with enzyme saline solutions, deionized water, and 50% (v/v) aqueous acetone solution. Caffeic, quinic, gallic, and ellagic acids, isomers of myricetin, catechin, and anthocyanins are bioaccessible during gastric digestion. In the duodenum, flavonoids and proanthocyanidins remained stable when the pH changed from acidic to neutral/alkaline, whereas anthocyanins were degraded when exposed to pH 7. In the colon, anthocyanins were not identified. The antioxidant activity of bioaccessible fractions is correlated with non-anthocyanin flavonoids and proanthocyanidins, reflected in the modulation of antioxidant enzymes of S. cerevisiae. The digestion process favors the release of bio-polyphenols from jambolan with preventive, scavenger, and reparative antioxidant action. They also stimulate the production and activity of Sod and Cat, strengthening the endogenous antioxidant system.

Phytochemical screening, phenolic and flavonoid contents, antioxidant and cytogenotoxicity activities of Combretum leprosum Mart. (Combretaceae).

Combretum leprosum Mart. (Combretaceae), a shrub popularly known as mofumbo, is used in folk medicine for treatment of uterine bleeding, pertussis, gastric pain, and as a sedative. The aim of this study was to (1) determine the phytochemical profile,(2) identify chemical constituents and (3) examine antioxidant and cytogenotoxic activity of ethanolic extracts and fractions of stem bark and leaves. The plant material (leaf and stem bark) was submitted to extraction with ethanol, followed by partition using hexane, chloroform, and ethyl acetate. It was possible to identify and quantify the epicatechin in the ethanolic stem bark extract (0.065 mg/g extract) and rutin in the leaf extract (3.33 mg/g extract). Based upon in vitro tests a significant relationship was noted between findings from antioxidant tests and levels of total phenolic and flavonoid. Comparing all samples (extracts and fractions), the ethyl acetate fractions of stem bark (411.40 ± 15.38 GAE/g) and leaves (225.49 ± 9.47 GAE/g) exhibited higher phenolic content, whereas hexanic fraction of stem bark (124.28 ± 56 mg/g sample) and ethyl acetate fraction of leaves (238.91 ± 1.73 mg/g sample) demonstrated a higher content of flavonoids. Among the antioxidant tests, the intermediate fraction of stem bark (28.5 ± 0.60 µg/ml) and ethyl acetate fraction of leaves (40 ± 0.56 µg/ml) displayed a higher % inhibition of free radical DPPH activity, whereas intermediate fraction of stem bark (27.5 ± 0.9 µg/ml) and hydromethanol fraction of leaves (81 ± 1.4 µg/ml) demonstrated inhibition of the free radical ABTS. In biological tests (Allium cepa and micronucleus in peripheral blood), data showed that none of the tested concentrations of ethanolic extracts of leaves and stem bark produced significant cytotoxicity, genotoxicity, and mutagenic activity.Abbreviations AA%: percentage of antioxidant activity; ABTS: 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid); CEUA: Ethics Committee in the Use of Animals; TLC: Thin Layer Chromatography; DNA: deoxyribonucleic acid; DPPH: 1,1-diphenyl-2-picrylhydrazyl; ROS: Reactive oxygen species; EEB: ethanol extract of the stem bark; HFB: Hexanic fraction of stem bark; IFB: Intermediate fraction of stem bark; CFB: Chloroform fraction of stem bark; EAFB: Ethyl acetate fraction of stem bark; HMFB: Hydromethanol fraction of the stem bark; EEL: Ethanol extract from leaves; HFL: Hexane fraction of leaves; CFL: Chloroform fraction of leaves; EAFL: Ethyl acetate fraction of leaves; HMFL: Hydromethanol fraction of leaves; GAE: Gallic Acid Equivalent; IC50: 50% inhibition concentration; HCOOH: Formic acid; HCl: hydrochloric acid; HPLC: High-performance liquid chromatography; MN: micronucleus; WHO: World Health Organization; UFLC: Ultra-Fast Liquid Chromatography; UESPI: State University of Piauí.

Garcinielliptone FC: Selective anti-amastigote and immunomodulatory effects on macrophages infected by Leishmania amazonensis.

The present study was directed to the in vitro antileishmanial, cytotoxic and immunomodulatory effects of Garcinielliptone FC (GFC) against promastigote and macrophage-internalized amastigote forms of Leishmania amazonensis. GFC showed in vitro cytotoxicity against BALB/c peritoneal macrophages with CC50 of 74.90 µM. The hemolytic activity against sheep erythrocytes only demonstrated a decrease of 20.42% in cell viability at the highest tested concentration tested (1326.0 µM). GFC promoted in vitro growth inhibition of both promastigote and intracellular amastigotes with IC50 values of 14.06 and 1.91 µM, respectively, with 7.3-fold higher Selectivity Index (SI) for intracellular amastigotes (SI = 39.21) than for promastigotes (SI = 5.33). Interestingly, the pre-treatment of macrophages or promastigotes with GFC promoted decrease of infected macrophages and number of recovered amastigotes, respectively. Also, GFC was able to markedly promote macrophages activation by increase of phagocytic capability and nitrite production at concentrations able to solve infection of macrophages by L. amazonensis, suggesting the possible involvement of immunomodulatory modulation of macrophages leading to solve the infection. GFC is an emerging and promising chemical compound for the studies focused on the assessment of its therapeutic potential on in vivo experimental models of leishmaniasis.

Pharmaceutical development of tablets containing a spray-dried optimized extract from Lippia origanoides H. B. K.: influence of excipients and toxicological assessment

ABSTRACT Lippia origanoides is a honey shrub which has showed hypotensive potential assessed by in vivo studies. The aim of this work is the development of a pharmaceutical formulation composed by an optimized extract obtained from aerial parts of L. origanoides. The quantification of the naringenin marker in the dry extract and tablets developed was performed, as well as the assessment of the oral acute toxicity in rats. The hydroalcoholic extract of L. origanoides was spray-dried with the addition of colloidal silicon dioxide (Lo-HAE/CSD), and then applied in the preparation of eight different lots of tablets. The influence of the diluent (cellulose or babassu mesocarp), the presence of binder, and the percentage of lubricant, as well as organoleptic and physicochemical characteristics were screened. For the quantification of the marker content both in Lo-HAE/CSD and in the tablets, an analytical curve of the naringenin standard was fitted, and the samples were then analyzed in UFLC. The toxicological assessment was performed in female Wistar rats according to the Acute Toxic Class Method from OECD. The developed tablets produced meet acceptable macroscopic characteristics, and the presence of babassu as diluent provided improved physicochemical properties. The best content of Lo-HAE/CSD in the tablet (100.27%) was identified for the lot containing babassu, composed by 1.0% magnesium stearate, without PVP binder in its formulation. Moreover, Lo-HAE/CSD showed no signs of toxicity. Therefore, the babassu mesocarp powder is a promising pharmaceutical excipient for the development of herbal tablets containing the Lippia origanoides extract.

Volatile compounds and palynological analysis from pollen pots of stingless bees from the mid-north region of Brazil

ABSTRACT Samburá is the botanical pollen nectar agglutinated by salivary secretions of bees. Stingless bee pollen samples were collected in three periods of the year in Monsenhor Gil town, PI, Brazil, for extraction of volatile constituents by different techniques, analyzed by gas chromatography-mass spectrometry (GC-MS) and the palynological analysis used to identify the dominant pollen. Among the volatile compounds identified, kaur-16-ene, methyl and ethyl hexadecanoate, methyl linoleate and heneicosane were identified more frequently in the studied parameters: period of sample collection and extraction techniques used. The palynological analysis identified the pollen of Mimosa caesalpiniifolia Benth. as the dominant pollen in all samples studied.